Artificial antigen presenting cells that express prevalent HLA alleles: A step towards the broad application of antigen-specific adoptive cell therapies.

Overview

The artificial antigen-presenting cells (AAPCs) described in this review were generated to facilitate the production of virus-specific T-cells for the treatment of infections in patients after bone marrow transplant. These AAPCs consist of murine 3T3 cells genetically modified to express critical human molecules needed for T-cell stimulation, such as the co-stimulatory molecules B7.1, ICAM-1, and LFA-3 and one of a series of 6 common HLA class I alleles. When T-cells were sensitized against cytomegalovirus (CMV) using AAPCs that express a shared HLA allele or using autologous antigen-presenting cells (APCs) loaded with the CMVpp65 antigen, they were activated and expanded to become HLA-restricted CMVpp65-specific T-cells. These T-cells demonstrated functional activity in vitro against CMV by producing IFN-gamma and inducing CMVpp65-specific cytotoxicity. T-cells sensitized with AAPCs recognized antigenic epitopes presented by each HLA allele known to be immunogenic in Man. Sensitization with AAPCs also permitted expansion of IFN-gamma+ cytotoxic T-cells against subdominant epitopes that were not effectively recognized by T-cells sensitized with autologous APCs. This panel of AAPCs provides a source of immediately accessible, standardizable, and replenishable "off the shelf" cellular reagents with the potential to make adoptive immunotherapy widely available for the treatment of lethal infections, cancer, and autoimmune diseases.